Hydrochloric Acid → HCID 59475969, compound

HRID 1470055Notes

Reaction equation

HRID 1470055 reaction equation
[Li][CH2:2]CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[C:9]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH:8]=1.C[Si](C)(C)[O:25][C@@H:26]1[C@@H:31]([O:32][Si](C)(C)C)[C@H:30]([O:37][Si](C)(C)C)[C@@H:29]([CH2:42][O:43][Si](C)(C)C)[O:28][C:27]1=[O:48].Cl.C(=O)(O)[O-].[Na+]>C1COCC1.C1(C)C=CC=CC=1.C1(C)C=CC=CC=1.CO>[Cl:13][C:10]1[CH:11]=[CH:12][C:7]([C@@:27]2([O:48][CH3:2])[C@H:26]([OH:25])[C@@H:31]([OH:32])[C@H:30]([OH:37])[C@@H:29]([CH2:42][OH:43])[O:28]2)=[CH:8][C:9]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 10994280(3R,4S,5R,6R)-3,4,5-Tris-trimethylsilanyloxy-6-trimethylsilanyloxymethyl-tetrahydro-pyran-2-onHCID 223285944-Bromo-1-chloro-2-(4-methoxybenzyl)benzeneHCID 178418339Butyllithium

Product 1

HCID 59475969HCID 59475969, compoundYield 101.3%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 22635083Tetrahydrofuran tolueneSolvent

Conditions

Temperature
-78 °C

Procedure

A cold (−78° C.) solution of n-BuLi (124 mL, 2.5 M in hexane, 0.310 mol) was added dropwise under argon to a solution of 4-bromo-1-chloro-2-(4-methoxybenzyl)benzene (80 g, 0.258 mol) in dry THF/toluene (1:2 (v/v), 480 mL) cooled at −78° C. at such a rate as to keep the reaction temperature below −70° C. After the addition, the mixture was stirred for 40 min before transferred by a cannula to a stirred solution of (3R,4S,5R,6R)-3,4,5-tris(trimethylsilyloxy)-6-((trimethylsilyloxy)methyl)tetrahydro-2H-pyran-2-one (157 g, 0.335 mol) in toluene (480 mL) precooled to −78° C. at a rate as to keep the internal temperature below −70° C. The mixture was stirred for 3 h at −78° C. until starting material was consumed and was quenched slowly by hydrochloric acid (36-38%, 47.3 mL, 0.567 mol) in methanol (320 mL), keeping the internal temperature below −45° C. The reaction mixture was gradually warmed to room temperature and stirred overnight. The mixture was neutralized with saturated sodium bicarbonate aqueous solution to pH 7.5. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (2×1.0 L). The combined organic layers were washed with brine (2×1.0 L), dried over sodium sulfate, and concentrated. The residue was dried under vacuum at 40° C. to give the crude product as an off-white solid (111 g), which was used in the next step without further purification. Purity (HPLC) 66% (UV); MS ESI (m/z) 425[M+1]+.

Workup

  1. customthe reaction temperature below −70° C
  2. additionAfter the addition
  3. customprecooled to −78° C. at a rate
  4. customthe internal temperature below −70° C
  5. stirringThe mixture was stirred for 3 h at −78° C.
  6. customwas consumed
  7. customthe internal temperature below −45° C
  8. temperatureThe reaction mixture was gradually warmed to room temperature
  9. stirringstirred overnight
  10. customThe organic layer was separated
  11. extractionthe aqueous phase was extracted with ethyl acetate (2×1.0 L)
  12. washThe combined organic layers were washed with brine (2×1.0 L)
  13. dry with materialdried over sodium sulfate
  14. concentrationconcentrated
  15. customThe residue was dried under vacuum at 40° C.

Sources & evidence

ORD record
ord-577d1b7409ad448a86752465622db953
Source dataset
uspto-grants-2015_04
Patent number
US09006403B2

Reaction notes

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